Biomarkers of subclinical atherosclerosis

Abstract

The present invention relates to PIGR, APOA, HPT, HEP2, C5, ITIH1 and IGHA2 as biomarkers for the screening, diagnosis and/or monitoring of subclinical atherosclerosis and methods and kits using thereof.

1 . A method for the screening, diagnosis and/or monitoring of subclinical atherosclerosis in a subject, wherein said method comprises:
 a) determining in a biological sample isolated from said subject the protein expression levels of:
 i. PIGR and/or IGHA2; and 
 ii. optionally, one, two, three, four or five biomarkers, selected from APOA, HPT, HEP2, ITIH1 and C5; 
   b) comparing the levels of the biomarkers with a reference value;   c) wherein when the levels in the subject's sample of PIGR, IGHA2, APOA, HPT, HEP2 ITIH1 and/or C5 are increased with respect to the corresponding reference value is indicative of subclinical atherosclerosis.   
     
     
         2 . The method according to  claim 1 , wherein step a) comprises determining the protein expression levels of PIGR and/or IGHA2; and one, two, three, four or five biomarkers selected from the list consisting of APOA, HPT, HEP2, ITIH1 and C5. 
     
     
         3 . The method according to  claim 1 , wherein step a) comprises determining the protein expression levels of a plurality of biomarkers selected from the group consisting of:
 a. PIGR and/or IGHA2, and APOA;   b. PIGR and/or IGHA2, and HPT;   c. PIGR and/or IGHA2, and HEP2;   d. PIGR and/or IGHA2, and C5;   e. PIGR and/or IGHA2, and ITIH1;   f. PIGR and/or IGHA2, APOA and HPT;   g. PIGR and/or IGHA2, APOA and HEP2;   h. PIGR and/or IGHA2, APOA and C5;   i. PIGR and/or IGHA2, APOA and ITIH1;   j. PIGR and/or IGHA2, HPT and HEP2;   k. PIGR and/or IGHA2, HPT and C5;   l. PIGR and/or IGHA2, HPT and ITIH1;   m. PIGR and/or IGHA2, HEP2 and C5;   n. PIGR and/or IGHA2, HEP2 and ITIH1;   o. PIGR and/or IGHA2, APOA, HPT and C5;   p. PIGR and/or IGHA2, APOA, HPT and ITIH1;   q. PIGR and/or IGHA2, APOA, HEP2 and C5;   r. PIGR and/or IGHA2, APOA, HEP2 and ITIH1;   s. PIGR and/or IGHA2, HPT, HEP2 and C5;   t. PIGR and/or IGHA2, HPT, HEP2 and ITIH1; and   u. PIGR and/or IGHA2, APOA, HPT and HEP2.   
     
     
         4 . The method according to  claim 1 , wherein said method further comprises determining in said biological sample the protein expression levels of IGHG1; wherein when the levels of IGHG1 in the subject's sample are decreased with respect to a reference value is indicative of subclinical atherosclerosis. 
     
     
         5 . The method according to  claim 1 , wherein IGHA2 levels are relative levels with respect to any of IGHA1, IGHG1, IGHG2 or a combination thereof. 
     
     
         6 . The method according to  claim 1 , wherein said method further comprises conducting a traditional cardiovascular risk score. 
     
     
         7 . The method according to  claim 1 , wherein said method is a method for the screening and/or diagnosis of subclinical atherosclerosis in a subject classified as low risk when conducting a traditional cardiovascular risk score. 
     
     
         8 . The method according to  claim 1 , wherein said biological sample isolated from the subject is a serum, blood or plasma sample. 
     
     
         9 . The method according to  claim 1 , wherein said subject is a human subject. 
     
     
         10 . The method according to  claim 1 , wherein steps b) and/or c) are implemented by a computer. 
     
     
         11 . A data-processing apparatus comprising means for carrying out the steps of a method of  claim 10 . 
     
     
         12 . A computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out the steps of the method of  claim 10 . 
     
     
         13 . A computer-readable storage medium having stored thereon a computer program according to  claim 12 . 
     
     
         14 . Kit comprising reagents adequate for the determination of the protein expression levels of the following biomarkers:
 i. PIGR and/or IGHA2;   ii. optionally, one, two, three, four or five biomarkers selected from APOA, HPT, HEP2, ITIH1 and C5;   wherein said kit comprises:   a. an affinity reagent for PIGR and/or IGHA2;   b. optionally, an affinity reagent for one, two, three four or five of APOA, HPT, HEP2, ITIH1 and C5;   c. optionally, further comprising instructions for the use of said reagents in determining said protein expression levels in a biological sample isolated from a subject.   
     
     
         15 . (canceled) 
     
     
         16 . The method according to  claim 1 , wherein the subclinical atherosclerosis is generalized subclinical atherosclerosis. 
     
     
         17 . The method according to  claim 5 , wherein IGHA2 levels are relative levels with respect to IGHA1 or with respect to the average levels of IGHG1 and IGHG2. 
     
     
         18 . The method according to  claim 6 , wherein said traditional cardiovascular risk score is selected from the group consisting of 10-y FHS, 30-y FHS, ICHS and the BEWAT scores. 
     
     
         19 . The method according to  claim 18 , wherein said traditional cardiovascular risk score is 10-y FHS. 
     
     
         20 . The method according to  claim 10 , wherein, said biological sample is a serum sample. 
     
     
         21 . The method according to  claim 1 , wherein said method further comprises determining in said biological sample the protein expression levels of IGHA1 and IGHG2; wherein when the levels of IGHG1 in the subject's sample are decreased with respect to a reference value is indicative of subclinical atherosclerosis.